反应详情

温度

90 °C

Ethyl 3,5-dibromo-4-cyanothiophene-2-carboxylate (0.360 g, 1.06 mmol), cesium carbonate (1.05 g, 3.21 mmol), 2-hydroxymethylmorpholine (137 mg, 1.17 mmol), and tetrahydrofuran (4.5 mL, 36 mmol) were combined in a 15 mL pressure vessel equipped with a stir bar. The vessel was sealed, and the r×n was heated @ 90° C. with stirring for 4 hours. The reaction was cooled to rt. The r×n was poured into water/saline. The reaction vessel was washed out with additional water, then ethyl acetate, and these were added to the quench which was then transferred to a separatory funnel. The aqueous layer was extracted 3× with EtOAc. The extracts were combined, washed with saline, dried over Na2SO4, filtered, added Celite, concentrated in vacuo, and dried on high vac 30 min. Purified dry load via silica gel chromatography (gradient elution: 0-60% EtOAc/hexanes) to give 163 mg solid (41% yield). 1H NMR (400 MHz, DMSO) δ 4.91 (t, J=5.7 Hz, 1H), 4.25 (q, J=7.1 Hz, 2H), 3.99-3.92 (m, 3H), 3.69-3.58 (m, 2H), 3.50 (dt, J=10.5, 5.2 Hz, 1H), 3.41 (dt, J=11.5, 5.8 Hz, 1H), 3.37-3.27 (m, 1H, under H2O peak), 3.15-3.08 (m, 1H), 1.26 (t, J=7.1 Hz, 3H).

1. customequipped with a stir bar
2. customThe vessel was sealed
3. temperatureThe reaction was cooled to rt
4. washThe reaction vessel was washed out with additional water
5. additionethyl acetate, and these were added to the
6. customquench which
7. customwas then transferred to a separatory funnel
8. extractionThe aqueous layer was extracted 3× with EtOAc
9. washwashed with saline
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. additionadded Celite
13. concentrationconcentrated in vacuo
14. customdried on high vac 30 min
15. customPurified
16. customdry load
17. washvia silica gel chromatography (gradient elution: 0-60% EtOAc/hexanes)